The morphologic characteristics and pathogenesis of renal glomerulosclerosis and of retinal microvascular disease in chemically-induced diabetes mellitus in rats complicated by experimentally-induced uremia and/or hypertension shall be examined. The reversibility of these lesions by transplantation of the islets of Langerhans shall be examined. The role of growth hormone in the pathogenesis of microvascular disease will be examined by the induction of diabetes mellitus in growth hormone deficient mice. Chemical measurements will include blood levels of glucose, insulin, growth hormone, urea nitrogen and creatinine plus renal creatinine clearance plus urinary albumin measurement. The reversibility of glomerulosclerosis, of renal tubulopathy and of retinal capillary pathology after islet transplantation will be studied by light microscopy, fluorescent microscopy for the presence of plasma proteins in involved tissues, and by electron microscopy, the latter including quantitative evaluation of glomerular cellular and membrane components and of cellular and basement membrane changes in retinal capillaries of the outer plexiform layer. The metabolism of radiolabeled and fluorescein-labeled aggregated human IgG by glomerular and renal tubules will be examined in states of diabetes, uremia, unilateral nephrectomy, hypertension and unilateral renal ligation. The control of renal renin will be examined in the above models by NaCl loading and deprivation in the above conditions in chemically-induced diabetes mellitus in rats as well as in spontaneous diabetes in genetically obese-diabetic hyperinsulinemic mice. These experiments will attempt to reproduce the clinical situation as it is present in humans with diabetic microvascular disease.